Nitric oxide-induced blood-brain barrier dysfunction is not mediated by inhibition of mitochondrial respiratory chain activity and/or energy depletion

The six reported cases were separated into 2 groups: 1) the tumors of sporadic type, carcinoids (n = 2) and neuro-endocrine carcinomas (n = 2); 2) the gastrin-promoted tumors (n = 2). The purpose of this retrospective study was to review for each group of tumors, the clinicopathologic characteristics, prognosis factors and optimal management. In the first group, patients with a small and well differentiated tumor revealed by digestive bleeding, were treated by wedge excision and are alive and well 24 and 22 years later; the patients with large, invasive and poorly differentiated tumors were treated by subtotal (n = 1) and total (n = 1) gastrectomy, and died 1 year and 3 years later with metastases. In the second group, one patient with a small asymptomatic carcinoid tumor revealing chronic atrophic gastritis, was treated by endoscopic resection, without recurrence 3 years later; another patient with asymptomatic multifocal carcinoid tumors (about 100) associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1, was treated by total gastrectomy and is alive and well 7 years later. No patient had carcinoid syndrome. Synaptophysin was the most sensitive marker and secretion of serotonine was detected in 2 tumors. Conclusion: Sporadic carcinoids serotonin and neuro-endocrine carcinomas are life-threatening tumors and need aggressive surgical therapy: their prognosis depends on tumors size, histological differentiation and mostly on tumor extension. In contrast, gastrin-promoted carcinoids do not result in disseminated disease and death, and a rather conservative approach seems appropriate.     

Five-year follow-up of a prospective randomised multi-centre trial of weekly chemotherapy (CAPOMEt) versus cyclical chemotherapy (CHOP-Mtx) in the treatment of aggressive non-Hodgkin''s lymphoma. Central Lymphoma Group

Benign tumors of the pancreatic head are normally treated by a partial duodenopancreatectomy. This operation has been developed for the treatment of malignant alterations in the pancreatic head and includes resection of the gastric bowel, duodenum and common bile duct. The aim of this study was to evaluate whether the less radical duodenum-preserving pancreatic head resection is a suitable surgical procedure in the treatment of benign pancreatic head tumors. From May 1982 to December 1996, seven patients underwent surgical treatment for benign pancreatic head tumors. Two patients suffered from gastrinoma of the pancreatic head, four exhibited a serous or mucinous cystadenoma, and one patient suffered from an intraductal papillary-mucinous tumor in this region. All patients were treated by duodenum-preserving pancreatic head resection. The operation was easily performed with little blood loss and a low rate of complications. None of the patients had to be reoperated upon due to postoperative surgical complications. After a follow-up period of a median 3 years, six of seven patients were had no recurrence of the disease and were symptom-free. One patient who had initially been operated on for gastrinoma still exhibited high gastrin values postoperatively. The endocrine and exocrine pancreatic function was not impaired in the early and late postoperative phase as compared to the preoperative assessment. From our results, it is concluded that duodenum-preserving pancreatic head resection is an adequately radical, yet organ-preserving procedure for the treatment of benign tumors of the pancreatic head without compromising endocrine and exocrine function.     

Primary bone and metastatic tumors of the cervical spine

Cervical spine tumors, whether primary bone tumors or metastatic tumors, are rare. The possibility of tumors existing must be considered in the differential diagnosis of patients with persistent neck pain, with or without neurologic symptoms, particularly in those with significant pain at night. The clinical presentation is extremely variable, though a history of malignancy should always raise the concern for recurrence. The evaluation and diagnostic assessment includes a thorough physical examination. Radiographic imaging is usually initiated with plain radiographs and additional advanced imaging obtained as indicated. Using appropriate biopsy principles and techniques, tissue is obtained for histologic determination of the suspected lesion before surgical intervention. Treatment options are extremely variable and depend on many factors, including tumor type, location, and patient preference. Treatment warrants a multidisciplinary approach from experienced physicians and is most successfully accomplished in referral centers. Oncologic staging using the Enneking staging system, followed by surgical staging using the Weinstein, Boriani, Biagini system, will aid in the accurate characterization of the tumor load, maximize surgical goals, assure use of appropriate terminology, and provide optimal communication among treatment centers regarding tumor characteristics, treatment efforts, and results.     

Advances in magnetic resonance imaging: applications in body imaging

Recent developments in the field of endocrine cell biology and pathology at both morphological and molecular levels are briefly outlined and discussed as a basis for endocrine tumor characterization. The main tools available for identifying the endocrine nature of the tumors, their pathogenetic interpretation. and experimental reproduction with special emphasis on tumor antecedents are reported. Based on this, classifications of endocrine tumors of the pancreas and gastrointestinal tract are developed, covering most clinical (hyperfunctional syndromes included), pathological, and biological patterns, with special emphasis on tumor prognosis.     

Zollinger-Ellison syndrome. Improved treatment options for this complex disorder

Zollinger-Ellison syndrome is a rare disorder characterized by severe peptic ulcer disease, gastric acid hypersecretion, and non-beta islet cell tumors of the pancreas. Most gastrinomas are found within an anatomic area known as the gastrinoma triangle. However, they commonly occur in extrapancreatic sites in multiple endocrine neoplasia type 1 syndrome. In patients in whom Zollinger-Ellison syndrome is suspected, laboratory evidence of hypergastrinemia and hyperacidity establishes the diagnosis. Until the advent of proton pump inhibitors, total gastrectomy was the treatment of choice. Therapy with these agents (eg, omeprazole, lansoprazole) can prevent ulcer disease. However, surgical removal of gastrinomas offers a chance for cure and can improve longevity by preventing the malignant spread of the tumors.     

Mutation of the MENIN gene in sporadic pancreatic endocrine tumors

Pancreatic endocrine tumors occur both sporadically and as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome. MEN1 is an autosomal dominant disease characterized by parathyroid hyperplasia, pancreatic endocrine tumors, and pituitary adenomas. The MEN1 gene called MENIN maps to chromosome 11q13 and is thought to function as a tumor suppressor gene. We previously demonstrated loss of heterozygosity (LOH) at 11q13 in approximately 40% of sporadic pancreatic endocrine tumors and hypothesize that MENIN is involved in the development of these tumors. Thirty-one sporadic pancreatic endocrine tumors were analyzed for mutation of MENIN by nonradioactive single-stranded conformation polymorphism. Twelve mutations were detected in 31 sporadic pancreatic endocrine tumors (34%). Twelve of these 31 tumors previously demonstrated loss of heterozygosity at 11q13. Of the tumors with LOH, seven contained mutations of the MENIN gene (58%). The majority of the MENIN mutations occurred within exon 2. Two independent mutations in MENIN were detected in a gastrinoma that also revealed LOH, leading to the possibility of another tumor suppressor gene locus at 11q13. Mutations were present in both benign and malignant pancreatic endocrine tumors, suggesting that a MENIN gene mutation is a frequent and early event in the tumorigenesis. The high incidence of truncating mutations in tumors with LOH at 11q13 support the hypothesis that MENIN is a tumor suppressor gene.     

Can total thyroidectomy be performed as safely by general surgeons in provincial centers as by surgeons in specialized endocrine surgical units? Making the case for surgical training

OBJECTIVE: To determine whether surgeons who had received appropriate training in the technique of total thyroidectomy could continue to perform the procedure with minimal morbidity after moving to a provincial surgical practice. DESIGN: Comparison of the complication rates from total thyroidectomy between a specialized endocrine surgical unit and provincial centers. SETTING AND PATIENTS: Six hundred fifty patients undergoing total thyroidectomy by two surgeons over a 5-year period in the endocrine surgical unit at Royal North Shore Hospital, St Leonards, Australia, were compared with 120 patients undergoing total thyroidectomy by seven provincial surgeons who were former trainees in the unit. MAIN OUTCOME MEASURES: Indications for surgery and specific complications of thyroidectomy including recurrent laryngeal nerve palsy, permanent hypoparathyroidism, and postoperative bleeding. RESULTS: Each of the seven surgeons in provincial practice performed only between two and 16 thyroidectomies annually. The percentage of total thyroidectomies for benign and malignant disease was identical for both the endocrine surgical unit and provincial center groups (44%). There was no difference in the incidence of recurrent laryngeal nerve palsy, permanent hypoparathyroidism, or postoperative bleeding between the two groups. CONCLUSION: Total thyroidectomy is an operation that always engenders controversy relating to the morbidity of recurrent laryngeal nerve and parathyroid injury. Surgeons who have completed a well-designed training program and who have become proficient at total thyroidectomy as trainees will remain proficient at the procedure despite practicing in a provincial center. Achieving a low morbidity rate demands meticulous attention to operative technique and anatomical detail.     

The effect of anastrozole on the pharmacokinetics of tamoxifen in post-menopausal women with early breast cancer

Endocrine tumors, such as parathyroid adenomas and pheochromocytomas, frequently have deletions of chromosome 1, suggesting that inactivation of a tumor suppressor gene from chromosome 1 is important in their tumorigenesis. We hypothesized that deletion of chromosome 1 may contribute to pancreatic endocrine tumor formation. Twenty-nine sporadic and MEN1 pancreatic endocrine tumors were studied for loss of heterozygosity (LOH) with 12 chromosome 1 microsatellite markers. LOH on chromosome 1 was identified in 10 of 29 (34%) tumors studied. Allele loss occurred more frequently in tumors with hepatic metastases (7 of 8) than tumors without metastases (3 of 21) (P = 0.004). Tumors in patients with lymph node involvement and patients with multiple endocrine neoplasia type 1 did not demonstrate LOH for chromosome 1 markers. These data suggest that loss of chromosome 1 is associated specifically with the development of hepatic metastases in patients with sporadic pancreatic endocrine tumors.     

Gs alpha mutation may be uncommon in patients with multiple endocrine neoplasia type 1

Activating mutations of the Gs alpha gene, termed gsp, have been identified in various endocrine tumors. Recently, a high frequency of gsp mutation in patients with multiple endocrinopathies was reported, and a family with both McCune-Albright syndrome and multiple endocrine neoplasia type 1 was described. Each suggests that the oncogenic mutations of Gs alpha may play an important role in tumorigenesis in patients with multiple neoplastic endocrinopathies, and a search for the gsp mutation in multiple endocrine neoplasia type 1 (MEN1) should be undertaken. We, therefore, reevaluated the frequency of gsp mutations in endocrine tumors of patients with MEN1. Of 18 tumors from 13 patients with MEN1, we found no gsp mutations regardless of heredity. We conclude that the gsp mutation may be uncommon in endocrine tumors of MEN1 patients, and thus, this mutation plays little, if any, role in their tumorigenesis.     

Ultrastructural pattern of glucagon producing-cells in the gastric mucosa of the developing opossum Didelphis albiventris (Marsupialia)

We present the case of a 59-year-old woman with an International Federation of Gynecology and Obstetrics stage IIIB serous psammocarcinoma. Only 12 cases of this rare ovarian neoplasm have been reported previously. These tumors act like borderline tumors and, therefore, do not usually require chemotherapy or radiation therapy after appropriate surgical debulking and staging.     

Teaching and maintaining behavior management skills with nursing assistants in a nursing home

Since the first report of pancreatic endocrine tumors by Wilder et al. in 1927 and the development of radioimmunoassay of gut hormone by Berson and Yallow in 1961, Japanese clinicians and scientists have contributed significantly in the reporting, investigation, and management of patients with pancreatic endocrine tumors and other multiple endocrine neoplasia. This article summarizes our contribution in this field and contrasts our experiences with those reported in the English literature.     

Immunoreactivity and expression of amylin in gastroenteropancreatic endocrine tumors

Amylin was isolated from human insulinomas, but there has been only preliminary data regarding whether this peptide can also be detected in other types of gastroenteropancreatic endocrine tumors. In the present study, immunohistochemical staining of 87 gastroenteropancreatic endocrine tumors demonstrated amylin immunoreactivity in 21.8% of the neoplasmas. Thirteen of 15 insulinomas, three of 21 gastrinomas, two of 29 nonfunctioning tumors, and one of 18 carcinoids were amylin-immunoreactive. Seventeen of the 19 amylin-immunoreactive tumors were primarily located in the pancreas, but two tumors were found in the intestine. Measurements of amylin messenger RNA expression in a few tumors revealed amylin synthesis in these tumors. Amylin immunoreactivity did not correlate with invasion and metastasis. However, the rate of curative resections was significantly higher in amylin-immunoreactive tumors. These results demonstrate for the first time that amylin immunoreactivity is not restricted to insulinomas and can also occur rarely in endocrine tumors of the intestine.     

Limited tumor involvement found at multiple endocrine neoplasia type I pancreatic exploration: can it be predicted by preoperative tumor localization?

Radiologically demonstrable pancreatic endocrine tumors are a frequent requirement for exploration in patients with multiple endocrine neoplasia type I (MEN-I). Such delayed intervention is accompanied by a 30% to 50% incidence of pancreatic endocrine metastases. This study explores biochemical tumor markers and operative findings in relation to preoperative pancreatic radiology in 25 MEN-I patients. They underwent pancreatic surgery with (n = 19) or without (n = 6) radiologic signs of primary tumor and absence of metastases upon conventional examination, including OctreoScan testing (n = 10). Biochemical diagnosis required an increasing elevation of at least two independent pancreatic tumor markers. Tumor diameters averaged 1.1 cm (0-5 cm) and 0.9 cm (0.2-1.5 cm) in the patients with and without positive preoperative radiology, respectively. These investigations never displayed more than one of the consistently multiple tumors, and the results were falsely positive in 26%. Preoperatively unidentified regional or hepatic metastases were found at surgical exploration in 26% of patients with radiologic localization and in none of the others. Limited pancreatic tumor involvement necessitated intraoperative absence of metastases and pancreatic lesions /= 7 mm in diameter. Conventional pancreatic imaging is insensitive and nonspecific for recognizing even substantial pancreatic tumors associated with MEN-I.     

Management of patients and subjects at risk for multiple endocrine neoplasia type 1: MEN 1. GENEM 1. Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1

Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the combined occurrence, to variable degree, of hyperparathyroidism (HPT) (85.7% of cases according to the French Registry of GENEM 1), tumors of the endocrine pancreas (49.6%), pituitary adenomas (38.4%) and, less frequently, adrenal tumors (9.6%) and neuroendocrine tumors (5.8%). Currently, diagnosis of MEN 1 is done in the fourth decade of life, but familial screening (using genetic tools whose diagnostic accuracy approaches 100%) has lowered the age of diagnosis. Screening for MEN 1 in a patient harboring an apparently sporadic tumor will depend on the endocrine gland involved. Extensive screening for MEN 1 in the presence of HPT will be conducted only when the familial history is suggestive, when parathyroid glands are hyperplastic or when multiple parathyroid adenomas have been found at surgery. All patients with an endocrine pancreas tumor need to be investigated for the presence of other endocrine lesions of MEN 1. Extensive screening for MEN 1 is only recommended when a patient with a pituitary tumor or an adrenal tumor has a familial history suggestive of MEN 1. Otherwise regular measurement of blood calcium and PTH levels seem sufficient. Extensive screening for endocrine lesions when MEN 1 is suspected involves hormone measurements and imaging procedures. For the diagnosis of HPT, calcemia and PTH 1-84 must be measured. In the absence of clinical symptoms, basal measurement of serum gastrin, glucose, insulin, glucagon, VIP, somatostatin and pancreatic polypeptide levels are combined with abdominal ultrasonography. When symptoms suggest the Zollinger-Ellison syndrome, the secretin stimulation test is recommended. The diagnosis of a pituitary tumor is made by pituitary imaging and selected hormone assays (mainly PRL). To detect an adrenal tumor, CT scan is recommended, combined with serum potassium, urinary free cortisol and androgen measurement. When the diagnosis of MEN 1 is made, clinical and hormonal follow-up (once a year) and imaging surveillance (every 3-5 years) may be sufficient to detect new other endocrinopathies (unless suggestive clinical symptoms arise). Surgical management of each endocrine lesion must be done by skilled surgeons according to therapeutic protocols which have been discussed in detail. Genetic screening is an integral part of familial screening which may be conducted in collateral and in the offspring of MEN 1 patients. Obviously ethical principles (informed consent, etc.) must be respected. As it is now possible to detect presymptomatic gene carriers with a high degree of accuracy, follow-up is needed to make appropriate management decisions. The marked anxiety provoked by screening in an overtly asymptomatic healthy subject must not be underestimated. Conversely, a negative genetic diagnosis helps to reassure the subject and avoid repetitive and costly follow-up.     

Treatment of clinically localized prostatic cancer--endocrine therapy

We assessed the actuarial survival of 28 patients with localized prostate cancer who were treated with endocrine therapy in comparison with that of 19 patients who had radical prostatectomy between 1972 and 1995. There were no significant differences among the cause-specific curves and clinical disease-free survival of patients treated with endocrine therapy and radical prostatectomy but the all-cause survival curves favored the surgery group. The results of endocrine therapy alone were unsatisfactory for the patients with high grade tumors. In conclusion, the patients with localized prostate cancer at high risk of death from other complications are reasonable candidates for endocrine therapy.     

Chiasmal syndrome due to intrasellar abscess

A 43-year-old woman had diabetes insipidus and amenorrhea. There was panhypopituitarism on endocrine testing and visual field examination showed inexorably progressive loss to bitemporal hemianopsia. All radiographic findings were normal, but craniotomy disclosed the cause of this chiasmal syndrome to be an intrasellar abscess which, on culture, grew a Gram-positive anaerobe, Peptococcus. Intrasellar or pituitary abscess is rare, but it must always be considered in the differential diagnosis of the chiasmal syndrome, since loss of pituitary and visual function may occur much more rapidly than with the tumors most often responsible for this syndrome and since surgical cure is possible.     

Diagnostic and therapeutic strategy of insulinomas. Apropos of a personal experience of 21 cases

Insulinomas account for about 90% of all pancreatic endocrine tumors and their surgical resection leads to cure in 90% of patients. Although current laboratory tests have simplified the clinical diagnosis of insulinomas, despite recourse to an array of most preoperative diagnostic procedures in 10-15% of patients the exact location of the tumor remains undefined. Tumor localization is difficult because: 80% of insulinomas measure less than 2 cm, about 10-12% of insulinomas are multicentric and 4-6% escape detection because are multiple endocrine neoplasms (MEN). If preoperative imaging fails to detect the site of the lesion, the surgeon could be obliged to perform a "blinded resection" with high risks of failure. The Authors refer their experience in a series of 21 patients operated on for insulinoma over the past 8 years (1987-1995). Arteriography with calcium stimulation (ASVS) and scintigraphy with 111-Indium-labeled octreotide performed in the later 16 and 13 cases respectively, achieved a correct tumor localization (confirmed by surgery) in 100% and 84.7% of patients. Intraoperative ultrasonography, performed in 18 cases, allowed not only to localize the tumor but also to study the tumor's neighbouring anatomic structures (Wirsung duct. splenic artery and vein), thus providing the anatomical and surgical information necessary to plan the right surgical strategy (tumor enucleation or pancreatic resection). Tumor enucleation was performed in 15 patients, distal pancreatic resections in 5 cases and multiple liver biopsies in 1 case: this patient had liver micrometastases from a malignant insulinoma without a palpable tumor. Operative mortality was nil. Postoperative complications occurred only in 5 of the 15 enucleations (1 pseudocyst successfully treated with a ultrasound-guided drainage and 4 pancreatic fistula resolved by medical therapy).     

Intraoperative gastrin measurements during surgical management of patients with gastrinomas: experience with 20 cases

Despite recent advances in imaging techniques for endocrine tumors of the duodenum and the pancreas, preoperative localization of gastrinomas is inconsistent. Successful surgical management of patients with Zollinger-Ellison syndrome (ZES) and removal of all gastrin-secreting tumors remains a difficult task. The aim of the study was to evaluate the predictive value of intraoperative gastrin measurements for successful surgical treatment in patients with gastrinomas. Intraoperative gastrin measurements were performed in 20 patients with ZES who underwent resection of gastrin-secreting tumors. Gastrin was measured with a radioimmunologic assay in blood samples obtained from a peripheral vein and from the portal vein at the beginning of the operation (T0) and 20 minutes after removal of the lesion(s) (T1). In 16 patients gastrin was also measured 4 minutes after injection of secretin 3 U/kg (T2). Thirteen patients (65%) were cured by surgery. In two of them, peripheral and portal gastrin levels were normal at T0, precluding any further interpretation of the test. Completeness of surgery was confirmed by normalization of gastrin levels at T1 or the absence of stimulation at T2 (or both) in 10 patients. In only one case did the gastrin levels remain elevated at T1 despite a favorable outcome after surgery. In each of the seven patients (35%) who had persisting disease at 1 year, failure of the surgical procedure was predicted by persistence of high levels of gastrin at T1. In patients with hypergastrinemia, the positive predictive value of intraoperative gastrin measurement for completeness of surgery and the specificity were 100%. The negative predictive value was 88% and the sensitivity 91%. The overall accuracy of the test was 94%. In patients with ZES the normalization of systemic hypergastrinemia during surgery affirms the successful removal of all gastrin-secreting tumors. We conclude that intraoperative gastrin measurement is a valuable addendum for optimizing the surgical management of gastrinoma.     

Amyloid in polypeptide hormone-producing tumors

The hormone content of 72 endocrine tumors was determined by immunofluorescence and their amyloid content was investigated. Seventeen of the 72 tumors contained amyloid. Amyloid was frequently found in tumors producing calcitonin, insulin, or growth hormone, but was rarely found in other tumors. Thus, there is a relationship between the occurrence of amyloid in an endocrine tumor and the type of hormone it produces. The reason for this is not known, but there is evidence that the amyloid fibrils contain proteins related to the hormone produced by the tumors.     

Slow-release lanreotide treatment in endocrine gastrointestinal tumors

OBJECTIVES: Lanreotide is a somatostatin analogue whose activity persists for 10-14 days. In this study, we treated a group of patients with gastrointestinal endocrine tumors with lanreotide to assess its therapeutic efficacy and tolerability. METHODS: Eighteen patients, 12 male and six female, mean age 58 yr (range, 25-80 yr) were studied. Ten had carcinoid tumors, five had nonfunctioning endocrine tumors, two had glucagonomas, and the remaining one had a gastrinoma. All patients had somatostatin receptors, demonstrated by octreoscan scintigraphy. Lanreotide was administered intramuscularly at a dose of 30 mg every 10 days, for a mean of 12 months (range, 5-18 months). Fifteen of the 18 patients had been previously treated with octreotide. RESULTS: In patients with carcinoid tumors, lanreotide markedly reduced daily bowel movements and flushing episodes. A reduction was also observed in urinary serotonin and urinary 5-hydroxyindoleacetic acid, although it was not statistically significant. A marked reduction in symptoms, and in plasma glucagon and serum gastrin levels, was also observed in patients with glucagonoma and gastrinoma. In the five patients with nonfunctioning endocrine tumors, as in all the other 13 patients, no significant effects were noted in the size of the tumor. The administration of lanreotide did not cause side effects, apart from transient abdominal pain and pain at the injection site in two patients. Only in the patient with gastrinoma was lanreotide suspended, because of the appearance of attacks of marked hypoglycemia. In the 15 patients previously treated with octreotide, no differences in the effects were noted with lanreotide. CONCLUSIONS: Lanreotide has a satisfactory therapeutic efficacy and tolerability in the treatment of gastrointestinal endocrine tumors; its effects are similar to those of octreotide. However, unlike octreotide, it can be administered once every 10-14 days, instead of 2 or 3 times daily and for this reason, it is preferable in clinical practice.